The molecular structure of disulfiram and its complexation with silica. A quantum chemical study

Abstract The complexation between disulfiram, more commonly known by trade names such as Antabus or Antabuse, and amorphous silica was studied by quantum chemical calculations due to extensive adsorption observed experimentally. The conformational behavior of the drug molecule was studied computationally at molecular mechanics (MM), Hartree-Fock (HF)/6-31G∗ and DFT/B3LYP/TZVP level. Two almost equally stable conformers were observed with the energy difference of only 0.8 kJ/mol when comparing the Gibbs’ free energies (Δ G ) at 25 °C. The Mulliken and Lowdin charges and the charges based on an electrostatic potential fit (ESP) were studied at HF/6-31G∗ level. Protonation of the optimized structures and complexation with geminal silanols were studied at DFT/B3LYP/TZVP level of theory in combination with the MARI-J approximation. Three groups of protonated structures were obtained and the proton affinity of the most stable protonated structure was calculated to 957.6 kJ/mol. In the complexation study four different kinds of complexes did converge. The BSSE-corrected electronic complexation energy of the most stable complex was calculated to −13.6 kJ/mol.